Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Rosemont Pharmaceuticals Ltd, Rosemont House, Yorkdale Industrial Park, Braithwaite Street, Leeds, LS11 9XE, UK
Treatment should be directed to stabilise manic depressive illness rather than to establish early control of acute episodes.
Dosage must be individualised depending on serum lithium levels and clinical response. The dosage necessary to maintain serum lithium levels within the therapeutic range varies from patient to patient. The minimum effective dose should be sought and maintained.
For oral administration only.
A simple treatment schedule has been evolved which except for some minor variations should be followed whether using Li-Liquid therapeutically or prophylactically. The minor variations to this schedule depend on the elements of the illness being treated and these are described later.
1. In patients of average weight (70 kg) an initial total daily dose of 1018–3054mg Lithium citrate (equivalent to 400-1200mg Lithium carbonate which is 10-30ml of liquid) should be given in divided doses, in the morning and in the evening.
When changing between lithium preparations, serum lithium levels should first be checked, then Li-liquid therapy commenced at a daily dose as close as possible to that of the other form of lithium. As bioavailability varies from product to product (particularly with regard to slow release preparations) a change of product should be regarded as initiation of new treatment.
2. Four to five days after starting treatment (and never longer than one week) a blood sample should be taken for the estimation of serum lithium level. Optimal maintenance serum levels may vary from patient to patient.
3. The objective is to adjust the Li-liquid dose so as to maintain the serum lithium level permanently within the diurnal range of 0.5–1.0 mmol/L. Blood samples for measurement of serum lithium concentration should be taken before a dose is due and not less than 12 hours after the previous dose. ‘Target’ serum lithium concentration at 12 hours should be 0.5-0.8 mmol/L. Serum lithium levels should be monitored weekly until stabilisation is achieved. Levels of more than 1.5mmol/L must be avoided.
The liquid should be taken at the same time every day. A double dose to make up for a dose that has been missed should not be taken.
4. Lithium therapy should not be initiated unless adequate facilities for routine monitoring of serum concentrations are available. Following stabilisation of serum lithium levels, the period between subsequent estimations can be increased gradually but should not normally exceed two to three months. Additional measurements should be made following alteration of dosage, on development of intercurrent disease, signs of manic or depressive relapse, following significant changes in sodium or fluid intake, or if signs of lithium toxicity occur.
5. Whilst a high proportion of acutely ill patients may respond within three to seven days after the commencement of therapy with Li-Liquid, it should be continued through any recurrence of the affective disturbance. This is important as the full prophylactic effect may not occur for 6 to 12 months after the initiation of therapy.
6. In patients who show a positive response to therapy with Li-Liquid, treatment is likely to be long term. Careful clinical appraisal of the patient should be exercised throughout medication (see precautions).
7. If lithium is to be discontinued, particularly in cases of high doses, the dose should be reduced gradually.
It is recommended that the described treatment schedule is followed.
It is likely that a higher than normal intake of Li-Liquid may be necessary during an acute phase. As a general rule the monitoring should maintain serum levels at 0.8–1.2 mmol/l until acute symptoms have been controlled. In all other details the described treatment schedule is recommended. The dosage needed may vary from patient to patient. Serum lithium levels should be monitored (see above) and should not exceed 1.5 mmol/l. As soon as control of mania or depression is achieved, the serum lithium level should be determined and it may be necessary, dependent on the results, to lower the dose of Li-Liquid and to re-stabilise serum lithium levels to the prophylactic dose.
In elderly patients or those below 50 kg in weight, it is recommended that a starting dose of 509mg lithium citrate (equivalent to 200mg lithium carbonate which is 5ml of liquid) is taken in divided doses, in the morning and in the evening. Elderly patients may be more sensitive to undesirable effects of lithium and may also require lower doses in order to maintain normal serum lithium levels. It follows therefore that long term patients often require a reduction in dosage over a period of years.
Not recommended.
In patients with mild and moderate renal insufficiency treated with lithium, serum lithium levels must be closely monitored and the dose should be adjusted accordingly to maintain serum lithium levels within the recommended range (see Section 4.4).
Lithium is contraindicated in patients with severe renal insufficiency (see Section 4.3).
Any overdose in a patient who has been taking chronic lithium therapy should be regarded as potentially serious.
In patients with a raised lithium concentration, the risk of toxicity is greater in those with the following underlying medical conditions: hypertension; diabetes; congestive heart failure; chronic renal failure; schizophrenia; Addison’s disease.
A single acute overdose usually carries low risk and patients tend to show mild symptoms only, irrespective of their serum lithium concentration. However more severe symptoms may occur after a delay if lithium elimination is reduced because of renal impairment, particularly if a slow-release preparation has been taken. The fatal dose, in a single overdose, is probably over 5g.
If an acute overdose has been taken by a patient on chronic lithium therapy, this can lead to serious toxicity occurring even after a modest overdose as the extravascular tissues are already saturated with lithium.
Lithium toxicity can also occur in chronic accumulation for the following reasons:
Acute or chronic overdosage; dehydration e.g. due to intercurrent illness, deteriorating renal function, drug interactions, most commonly involving a thiazide diuretic or a non-steroidal anti-inflammatory drug (NSAID).
The onset of symptoms may be delayed, with peak effects not occurring for as long as 24 hours, especially in patients who are not receiving chronic lithium therapy or following the use of a sustained release preparation.
Symptoms of lithium intoxication include:
Mild: Nausea, diarrhoea, blurred vision, polyuria, light headedness, fine resting tremor, muscular weakness and drowsiness.
Moderate: Increasing confusion, blackouts, fasciculation and increased deep tendon reflexes, myoclonic twitches and jerks, choreoathetoid movements, urinary or faecal incontinence, increasing restlessness followed by stupor. Hypernatraemia.
Severe: Coma, convulsions, cerebellar signs, cardiac dysrhythmias including sino-atrial block, sinus and junctional bradycardia and first degree heart block. Hypotension or rarely hypertension, circulatory collapse and renal failure.
Gastrointestinal disorders: increasing anorexia and vomiting.
Nervous system disorders: Encephalopathy, cerebellar syndrome with symptoms such as muscle weakness, lack of coordination, drowsiness or lethargy, giddiness, ataxia, nystagmus, coarse tremor. Tinnitus, dysarthria, twitching, myoclonus, extrapyramidal disorders.
ECG changes (flat or inverted T waves, QT prolongation), AV block, dehydration and electrolyte disturbances.
At blood levels above 2-3 mmol/l, there may be a large output of dilute urine and renal insufficiency, with increasing confusion, convulsions, coma and death.
There is no specific antidote to lithium. In the event of lithium overdose, lithium should be discontinued and serum levels monitored closely. Diuretics should not be used (see section 4.5). All patients should be observed for a minimum of 24 hours. ECG should be monitored in symptomatic patients. Steps should be taken to correct hypotension. Supportive treatment should be initiated, which includes correction of fluid and electrolyte balance, if necessary.
Consider gastric lavage for non-sustained-release preparations if more than 4 g has been ingested by an adult within one hour or definite ingestion of a significant amount by a child. Slow-release tablets do not disintegrate in the stomach and most are too large to pass up a lavage tube. Gut decontamination is not useful for chronic accumulation. Activated charcoal does not adsorb lithium.
Haemodialysis is the treatment of choice for severe lithium intoxication (especially in patients manifesting with severe nervous system disorders) or in cases of overdose accompanied by renal impairment. Haemodialysis should be continued until there is no lithium in the serum or dialysis fluid.
Serum lithium levels should be monitored for at least a further week to take account of any possible rebound in serum lithium levels as a result of delayed diffusion from the body tissues.
In cases of acute on chronic overdose or in cases of chronic lithium toxicity if the lithium concentration is >4.0 mmol/L, discuss with your local poisons service.
Clinical improvement generally takes longer than reduction of serum lithium concentrations regardless of the method used.
24 months.
6 months opened.
Store above 4°C and protect from light.
Bottles: Amber (Type III) glass bottles with capacity of 150ml.
Closures: HDPE EPE wadded, tamper evident, child resistant.
Keep out of the sight and reach of children.
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